DOCSLIB.ORG

Alterations in LMTK2, MSMB and HNF1B Gene Expression Are Associated with the Development of Prostate Cancer BMC Cancer 2010, 10:315

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Alterations in LMTK2, MSMB and HNF1B Gene Expression Are Associated with the Development of Prostate Cancer BMC Cancer 2010, 10:315 Harries et al. BMC Cancer 2010, 10:315 http://www.biomedcentral.com/1471-2407/10/315 RESEARCH ARTICLE Open Access AlterationsResearch article in LMTK2, MSMB and HNF1B gene expression are associated with the development of prostate cancer Lorna W Harries*1, John RB Perry2, Paul McCullagh3 and Malcolm Crundwell4 Abstract Background: Genome wide association studies (GWAS) have identified several genetic variants that are associated with prostate cancer. Most of these variants, like other GWAS association signals, are located in non-coding regions of potential candidate genes, and thus could act at the level of the mRNA transcript. Methods: We measured the expression and isoform usage of seven prostate cancer candidate genes in benign and malignant prostate by real-time PCR, and correlated these factors with cancer status and genotype at the GWAS risk variants. Results: We determined that levels of LMTK2 transcripts in prostate adenocarcinomas were only 32% of those in benign tissues (p = 3.2 × 10-7), and that an independent effect of genotype at variant rs6465657 on LMTK2 expression in benign (n = 39) and malignant tissues (n = 21) was also evident (P = 0.002). We also identified that whilst HNF1B(C) and MSMB2 comprised the predominant isoforms in benign tissues (90% and 98% of total HNF1B or MSMB expression), HNF1B(B) and MSMB1 were predominant in malignant tissue (95% and 96% of total HNF1B or MSMB expression; P = 1.7 × 10-7 and 4 × 10-4 respectively), indicating major shifts in isoform usage. Conclusions: Our results indicate that the amount or nature of mRNA transcripts expressed from the LMTK2, HNF1B and MSMB candidate genes is altered in prostate cancer, and provides further evidence for a role for these genes in this disorder. The alterations in isoform usage we detect highlights the potential importance of alternative mRNA processing and moderation of mRNA stability as potentially important disease mechanisms. Background early onset cases of prostate cancer (< 55yrs) are caused Cancer of the prostate is the most common male malig- by inherited factors [2], highlighting the importance of nancy in the Western world, accounting for 25% of all genetics in this disorder. Early-onset prostate cancer that male UK cancers (taken from http://info.cancerre- aggregates in families is likely to result from the inheri- searchuk.org/cancerstats). Although survival rates are tance of rare genetic variants that have a large impact. increasing, cancer of the prostate remains the second Several strong risk factors have been identified from fam- most common cause of cancer death in UK men after ily studies which include mutations in the ELAC2, RNA- lung cancer. Several risk factors have been identified, the SEL and MSR1 genes involved in immune response [4] main factors being age [1], family history [2] and ethnic and the BRCA1 and BRCA2 genes involved in the devel- origin [3]. Prostate cancer is uncommon in men under 50 opment of breast cancer [5]. years old, but 80% of men aged over 80 years were found Despite increases in the understanding of the familial to have cancerous cells in their prostate at the time of forms of prostate cancer, the aetiology of the remaining death [1]. Estimates suggest that between 30 - 40% of all 60% of cases remains unclear. The advent of genome wide association studies (GWAS) has resulted in a dramatic * Correspondence: [email protected] increase in the number of susceptibility loci that have 1 Institute of Biomedical and Clinical Sciences, Peninsula NIHR Clinical Research Facility, University of Exeter, Peninsula Medical School, Barrack Road, Exeter, been associated with the development of prostate cancer Devon, UK (table 1). Four independent studies in the Icelandic, UK Full list of author information is available at the end of the article © 2010 Harries et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Harries et al. BMC Cancer 2010, 10:315 Page 2 of 12 http://www.biomedcentral.com/1471-2407/10/315 Table 1: Loci that have been identified as significant determinants of prostate cancer risk in four independent genome wide association studies. Gene Location Marker MAF Post replication P value Position within gene Source HNF1B 17q21.3 rs4430796 0.479 9.58 × 10-10 IVS2 [7,8,34] rs11649743 0.479 1.7 × 10-9 IVS4 MSMB 10q11.2 rs10993994 0.339 8.7 × 10-29 5' UTR [8,9] 7.31 × 10-13 LMTK2 17q25.3 rs6465657 0.438 1.1 × 10-9 IVS9 [9] SLC22A3 6q26-q27 rs9364554 0.233 5.5 × 10-10 IVS5 [9] CTBP2 10q26.13 rs4962416 0.229 1.70 × 10-7 IVS1 [8] MYEOV 11q13 rs10896449 0.492 1.76 × 10-9 Intergenic, 5' to gene [8] JAZF1 7p15.2-p15.1 rs10486567 0.267 2.14 × 10-6 IVS2 [8] MAF = minor allele frequency in the HapMap CEU population. and American populations have identified more than 20 tissues, and whether their expression was influenced by distinct genomic locations as being implicated in suscep- genotype at the GWAS risk variants. Seven genes were tibility to prostate cancer [6-9]. selected for study (figure 1). We measured the total or Many of the GWAS association signals identified are isoform specific gene expression of the JAZF1 (JAZF zinc located in regions of the genome that are not translated finger 1), CTBP2 (C-terminal binding protein 2), LMTK2 into protein. This may indicate that the associated marker (lemur tyrosine kinase 2), SLC22A3 (solute carrier family is in close linkage disequilibrium with an uncharacterised 22 extraneuronal monoamine transporter, member 3), variant in the protein coding region, or that the func- MYEOV (myeloma overexpressed), MSMB (microsemi- tional SNP may cause its effect by epigenetic or histone noprotein beta) and HNF1B (HNF homeobox 1 beta) in a modification. The other possibility is that the variant may cohort of 39 non-malignant benign prostatic hyperplasia act at the level of the messenger RNA. (BPH) samples and 21 prostate adenocarcinoma samples, There are several mechanisms by which variants in and correlated gene expression with cancer status and non-coding regions of the mRNA transcripts could affect with the genetic variants identified in the GWAS (table gene function. Firstly, if the variant lies in the promoter or 1). We demonstrate two of the eight variants are corre- 5' untranslated region of the transcript, it may interfere lated with gene expression levels in non-malignant pros- with the efficiency of transcription or translation, as has tate tissues, and that the presence of adenocarcinoma is been shown to be the case for several human and rodent associated with altered gene expression levels and differ- genes [10-12]. Variants located within the intronic ential expression of alternatively processed isoforms for sequences may interfere with mRNA splicing [13]. The three of the candidate genes in prostate tissue itself. production of aberrant splice products has previously been shown to be very important in the aetiology of can- Methods cer in general [14,15], but may contribute to the biologi- Subject Details cal heterogeneity of prostate cancer in particular [16]. The prostate samples in this study were obtained from Finally, polymorphisms located in the 3' untranslated the Exeter tissue bank, and comprised prostate chippings region may disrupt regulatory elements necessary for taken during routine transurethral resection of the pros- mRNA stability, interfere with regulation of translation tate (TURP). Both cancer and BPH groups originated by microRNAs or influence the polyadenylation dynam- from a population of older men treated for urological ics of the transcript [17-19]. problems at the Royal Devon and Exeter Hospital, Exeter, In this series of experiments, we sought to investigate UK and were predominantly of Caucasian origin. Sam- whether the genes suggested by the GWAS for prostate ples were flash frozen in liquid nitrogen upon removal, cancer were differentially expressed in malignant prostate and stored at -80°C until required. Subjects with benign Harries et al. BMC Cancer 2010, 10:315 Page 3 of 12 http://www.biomedcentral.com/1471-2407/10/315 1 2 3 4 JAZF1 (NM_175061) 1 2 3 4 5 6 7 8 9 10 SLC22A3 (NM_021977) 1 2 3 4 5 6 7 8 9 10 11 12 13 LMTK2 (NM_014916) 1 2 MYEOV (NM_138768) 1 2 3 4 MSMB1 (NM_002443) 1 2 4 MSMB2 (NM_138634) 1 2 3 4 5 6 7 8 9 HNF1B(A) (NM_000458) 1 2 3 4 5 6 7 8 9 HNF1B(B) (NM_001165923) 1 2 3 4 HNF1B(C) (NM_006481) 1a 2 3 4 5 6 7 8 9 10 11 CTBP2(1) (NM_001083914) 2b 4 5 6 7 8 9 10 11 CTBP2(2) (NM_022802) 1b 2 3 4 5 6 7 8 9 10 11 CTBP2(3) (NM_001329) 1c 2 3 4 5 6 7 8 9 10 11 CTBP2(4) (AK290390 ) Figure 1 Schematic representation of the structure of transcripts studied here. The structure of the JAZF1, SLC22A3, LMTK2, MYEOV, MSMB, HNF1B and CTBP2 mRNAs are represented here, together with their RefSeq ID numbers. Exons are represented by numbered grey boxes. The black box represents the section of exon 3 absent from isoform HNF1B(B). The section of intronic sequence present in HNF1B(C) is indicated by a hatched box. prostatic hyperplasia (n = 39) had no sign of prostate and Gleason scoring by dissection of the TURP chips and malignancy at the time the samples were taken, and none subsequent histological examination of tissue from either had received a subsequent diagnosis of prostate cancer 5 side of the sample used for RNA analysis.
Load more

Recommended publications
  • Contribution of MSMB Promoter Region Gene Polymorphism to Early-Onset Prostate Cancer Risk in Mexican Males
    www.oncotarget.com Oncotarget, 2019, Vol. 10, (No. 7), pp: 738-748 Research Paper Contribution of MSMB promoter region gene polymorphism to early-onset prostate cancer risk in Mexican males Silvia Juliana Trujillo-Cáceres1, Luisa Torres-Sánchez1, Ana I. Burguete-García2, Yaneth Citlalli Orbe Orihuela2, Ruth Argelia Vázquez-Salas3, Esmeralda Álvarez- Topete4 and Rocío Gómez4 1Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública (INSP), Cuernavaca, Morelos, Mexico 2Centro de Investigación en Enfermedades Infecciosas, INSP, Cuernavaca, Morelos, Mexico 3Conacyt-Centro de Investigación en Salud Poblacional, INSP, Cuernavaca, Morelos, Mexico 4Departamento de Toxicología, Cinvestav-IPN, Mexico City, Mexico Correspondence to: Luisa Torres-Sánchez, email: [email protected] Keywords: genetic polymorphisms; MSMB; prostate cancer; rs10993994; sexually transmitted diseases Received: July 13, 2018 Accepted: December 16, 2018 Published: January 22, 2019 Copyright: Trujillo-Cáceres et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Sexually transmitted infections and its contribution to prostate cancer (PC) development have been relevant in different populations. MSMB gene polymorphism (rs10993994) has exhibited an association both with PC as well as the susceptibility to sexually transmitted infections. Hitherto, these conditions have been not studied in Mexico yet, neither if sexually transmitted infections could modify the MSMB and PC association. Herein, socio-demographic features, sexually transmitted infections records, the reproductive backgrounds, and the genetic characterisation were analysed in 322 incident PC cases and 628 population healthy controls from Mexico City.
    [Show full text]
  • DF6720-MSMB Antibody
    Affinity Biosciences website:www.affbiotech.com order:[email protected] MSMB Antibody Cat.#: DF6720 Concn.: 1mg/ml Mol.Wt.: 13kDa Size: 50ul,100ul,200ul Source: Rabbit Clonality: Polyclonal Application: WB 1:500-1:2000, IHC 1:50-1:200, ELISA(peptide) 1:20000-1:40000 *The optimal dilutions should be determined by the end user. Reactivity: Human,Mouse Purification: The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific). Specificity: MSMB Antibody detects endogenous levels of total MSMB. Immunogen: A synthesized peptide derived from human MSMB, corresponding to a region within the internal amino acids. Uniprot: P08118 Description: The protein encoded by this gene is a member of the immunoglobulin binding factor family. It is synthesized by the epithelial cells of the prostate gland and secreted into the seminal plasma. This protein has inhibin-like activity. It may have a role as an autocrine paracrine factor in uterine, breast and other female reproductive tissues. The expression of the encoded protein is found to be decreased in prostate cancer. Two alternatively spliced transcript variants encoding different isoforms are described for this gene. The use of alternate polyadenylation sites has been found for this gene. Storage Condition and Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM Buffer: NaCl, 0.02% sodium azide and 50% glycerol.Store at -20 °C.Stable for 12 months from date of receipt. Western blot analysis of HepG2 cell lysates, using MSMB Antibody. The lane on the left was treated with the antigen- specific peptide. 1 / 2 Affinity Biosciences website:www.affbiotech.com order:[email protected] DF6720 at 1/100 staining Mouse liver tissue by IHC-P.
    [Show full text]
  • Association of Imputed Prostate Cancer Transcriptome with Disease Risk Reveals Novel Mechanisms
    Corrected: Author Correction ARTICLE https://doi.org/10.1038/s41467-019-10808-7 OPEN Association of imputed prostate cancer transcriptome with disease risk reveals novel mechanisms Nima C. Emami1,2, Linda Kachuri2, Travis J. Meyers2, Rajdeep Das3,4, Joshua D. Hoffman2, Thomas J. Hoffmann 2,5, Donglei Hu 5,6,7, Jun Shan8, Felix Y. Feng3,4,7, Elad Ziv5,6,7, Stephen K. Van Den Eeden 3,8 & John S. Witte1,2,3,5,7 1234567890():,; Here we train cis-regulatory models of prostate tissue gene expression and impute expression transcriptome-wide for 233,955 European ancestry men (14,616 prostate cancer (PrCa) cases, 219,339 controls) from two large cohorts. Among 12,014 genes evaluated in the UK Biobank, we identify 38 associated with PrCa, many replicating in the Kaiser Permanente RPGEH. We report the association of elevated TMPRSS2 expression with increased PrCa risk (independent of a previously-reported risk variant) and with increased tumoral expression of the TMPRSS2:ERG fusion-oncogene in The Cancer Genome Atlas, suggesting a novel germline-somatic interaction mechanism. Three novel genes, HOXA4, KLK1, and TIMM23, additionally replicate in the RPGEH cohort. Furthermore, 4 genes, MSMB, NCOA4, PCAT1, and PPP1R14A, are associated with PrCa in a trans-ethnic meta-analysis (N = 9117). Many genes exhibit evidence for allele-specific transcriptional activation by PrCa master-regulators (including androgen receptor) in Position Weight Matrix, Chip-Seq, and Hi-C experimental data, suggesting common regulatory mechanisms for the associated genes. 1 Program in Biological and Medical Informatics, University of California San Francisco, San Francisco, CA 94158, USA.
    [Show full text]
  • Novel Gene Signatures Predictive of Patient Recurrence-Free Survival and Castration Resistance in Prostate Cancer Jun A, Baotong Zhang, Zhiqian Zhang, Jin-Tang Dong
    Supplementary Materials: Novel Gene Signatures Predictive of Patient Recurrence-Free Survival and Castration Resistance in Prostate Cancer Jun A, Baotong Zhang, Zhiqian Zhang, Jin-Tang Dong Figure S1. Overlap differentially expressed genes (DEGs) between our study and previously re- ported microarray experiments. Figure S2. The diagnosis effectiveness of the six CRPCPS genes. ROC curves for the six CRPCPS genes in the training cohort (a) and the validation cohort (b). Cancers 2021, 13 S2 of S13 Figure S3. Evaluation of the CRPCPS in the internal validation cohort and the entire TCGA cohort. (a) Distribution of CRPCPS score (left), patients’ recurrent status (center), and expression profiles of the six CRPCPS genes (right) in the internal validation cohort. (b) Receiver operating character- istic (ROC) curves were used to evaluate the predictability of RFS at 3-, 5-, and 8-year by the CRPCPS score, Gleason score, and pathological tumor stage in the internal validation cohort. (c) Distribution of CRPCPS score (left), patients' survival status (center), and expression profiles of the six CRPCPS genes that constitute the CRPCPS (right) in the entire TCGA cohort. (d) Receiver oper- ating characteristic (ROC) curves were used to evaluate the predictability of RFS at 3-, 5-, and 8- year by the CRPCPS score, Gleason score, and pathological tumor stage in the entire TCGA cohort. Cancers 2021, 13 S3 of S13 Figure S4. Association of CRPCPS with tumor stage (a-d), Gleason score (e-h), and lymph node status (i-k) in different patient cohorts. Figure S5. Association of CRPCPS with patients’ age in the TCGA training cohort (a), the TCGA validation cohort (b), the entire TCGA cohort (c), the MSKCC cohort (d), the Cambridge cohort (GSE70768) (e), and the Belfast cohort (GSE116918) (f).
    [Show full text]
  • Overview of Research on Fusion Genes in Prostate Cancer
    2011 Review Article Overview of research on fusion genes in prostate cancer Chunjiao Song1,2, Huan Chen3 1Medical Research Center, Shaoxing People’s Hospital, Shaoxing University School of Medicine, Shaoxing 312000, China; 2Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing 312000, China; 3Key Laboratory of Microorganism Technology and Bioinformatics Research of Zhejiang Province, Zhejiang Institute of Microbiology, Hangzhou 310000, China Contributions: (I) Conception and design: C Song; (II) Administrative support: Shaoxing Municipal Health and Family Planning Science and Technology Innovation Project (2017CX004) and Shaoxing Public Welfare Applied Research Project (2018C30058); (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: C Song; (V) Data analysis and interpretation: H Chen; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Chunjiao Song. No. 568 Zhongxing Bei Road, Shaoxing 312000, China. Email: [email protected]. Abstract: Fusion genes are known to drive and promote carcinogenesis and cancer progression. In recent years, the rapid development of biotechnologies has led to the discovery of a large number of fusion genes in prostate cancer specimens. To further investigate them, we summarized the fusion genes. We searched related articles in PubMed, CNKI (Chinese National Knowledge Infrastructure) and other databases, and the data of 92 literatures were summarized after preliminary screening. In this review, we summarized approximated 400 fusion genes since the first specific fusion TMPRSS2-ERG was discovered in prostate cancer in 2005. Some of these are prostate cancer specific, some are high-frequency in the prostate cancer of a certain ethnic group. This is a summary of scientific research in related fields and suggests that some fusion genes may become biomarkers or the targets for individualized therapies.
    [Show full text]
  • Development of a Real-Time PCR Assay for the Detection of Blood, Saliva, and Semen Author(S): Cynthia B
    The author(s) shown below used Federal funding provided by the U.S. Department of Justice to prepare the following resource: Document Title: Development of a Real-time PCR Assay for the Detection of Blood, Saliva, and Semen Author(s): Cynthia B. Zeller, Ph.D. Document Number: 251633 Date Received: April 2018 Award Number: 2008-DN-BX-K137 This resource has not been published by the U.S. Department of Justice. This resource is being made publically available through the Office of Justice Programs’ National Criminal Justice Reference Service. Opinions or points of view expressed are those of the author(s) and do not necessarily reflect the official position or policies of the U.S. Department of Justice. NATIONAL INSTITUTE OF JUSTICE 2008-DN-BX-K137 Development of a Real-time PCR Assay for the Detection of Blood, Saliva and Semen Cynthia Zeller, Ph.D. [email protected] 410-704-2170 EIN: 526002033 DUNS: 143372741 Towson University College of Graduate Studies and Research and Fisher College of Science and Mathematics Department of Chemistry Forensic Science Program 8000 York Rd. Towson, MD 21252 PROJECT START DATE: November 1, 2008 FINAL REPORT February 28, 2013 Cynthia B. Zeller, Ph.D Principal Investigator 1 ABSTRACT During the process of forensic DNA genotyping, evidence containing potential DNA evidence undergoes serological screening to determine which body fluid, if any, it contains. The majority of the DNA genotyping process has under gone automation, leaving a bottleneck at the serological analysis stage. This is due in large part to the methods employed to identify body fluids. Since most of the commonly used assays test for the presence or function of a particular protein prevalent in a specific body fluid, these tests cannot be multiplexed and therefore can use a fairly large portion of a stain if multiple body fluids need to be identified.
    [Show full text]
  • 10Q11.22Q11.23 Deletions and Microdeletions
    Inform Network Support Rare Chromosome Disorder Support Group The Stables, Station Road West, Oxted, Surrey RH8 9EE, United Kingdom Tel: +44(0)1883 723356 [email protected] I www.rarechromo.org Join Unique for family links, information and support. Unique is a charity without government funding, existing entirely on donations and grants. If you can, please make a donation via our website at http://www.rarechromo.org/donate Please help us to help you! 10q11.22q11.23 Facebook groups www.facebook.com/groups/chromosome10disorder/ www.facebook.com/groups/152331614838414/ Deletions and Unique mentions other organisations’ message boards and websites to help families looking for information. This does not imply that we endorse their content or have any responsibility for it. Microdeletions This information guide is not a substitute for personal medical advice. Families should consult a medically qualified clinician in all matters relating to genetic diagnosis, management and health. Information on genetic changes is a very fast-moving field and while the information in this guide is believed to be the best available at the time of publication, some facts may later change. Unique does its best to keep abreast of changing information and to review its published guides as needed. This booklet was compiled by Unique (AP) and reviewed by Dr Corrina Powell, Specialist Registrar in Clinical Genetics, and Rosa Spencer- Tansley, Trainee Genetic Counsellor, Leicester Royal Infirmary Clinical Genetics Department ,UK. Version 1 2019 (AP) Copyright © Unique 2020 Rare Chromosome Disorder Support Group Charity Number 1110661 Registered in England and Wales Company Number 5460413 rarechromo.org 20 Genetic information Genetic information genetic Detailed 10q11.22q11.23 microdeletions Chromosome Position Important Microdeletion A 10q11.2q11.23 microdeletion is a rare genetic condition caused by the loss of a 10 Mb genes examples small piece of genetic material from one of the body’s 46 chromosomes – chromosome 10.
    [Show full text]
  • Prenatal Diagnosis of Small Supernumerary Marker Chromosome 10 by Array-Based Comparative Genomic Hybridization and Microdissected Chromosome Sequencing
    biomedicines Article Prenatal Diagnosis of Small Supernumerary Marker Chromosome 10 by Array-Based Comparative Genomic Hybridization and Microdissected Chromosome Sequencing Igor N. Lebedev 1,* , Tatyana V. Karamysheva 2 , Eugeny A. Elisaphenko 2, Alexey I. Makunin 3 , Daria I. Zhigalina 1, Maria E. Lopatkina 1 , Gleb V. Drozdov 1, Aleksander D. Cheremnykh 1, Natalia B. Torkhova 1, Gulnara N. Seitova 1, Stanislav A. Vasilyev 1 , Anna A. Kashevarova 1, Ludmila P. Nazarenko 1 and Nikolay B. Rubtsov 2,4 1 Tomsk National Research Medical Center, Research Institute of Medical Genetics, 634050 Tomsk, Russia; [email protected] (D.I.Z.); [email protected] (M.E.L.); [email protected] (G.V.D.); [email protected] (A.D.C.); [email protected] (N.B.T.); [email protected] (G.N.S.); [email protected] (S.A.V.); [email protected] (A.A.K.); [email protected] (L.P.N.) 2 Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; [email protected] (T.V.K.); [email protected] (E.A.E.); [email protected] (N.B.R.) 3 Wellcome Sanger Institute, Cambridge CB101SA, UK; [email protected] Citation: Lebedev, I.N.; Karamysheva, 4 Department of Cytology and Genetics, Novosibirsk State University, 630090 Novosibirsk, Russia T.V.; Elisaphenko, E.A.; Makunin, A.I.; * Correspondence: [email protected]; Tel.: +7-38-2251-1109 Zhigalina, D.I.; Lopatkina, M.E.; Drozdov, G.V.; Cheremnykh, A.D.; Abstract: Interpreting the clinical significance of small supernumerary marker chromosomes (sSMCs) Torkhova, N.B.; Seitova, G.N.; et al.
    [Show full text]
  • The Percentage of Free PSA and Urinary Markers Distinguish Prostate Cancer from Benign Hyperplasia and Contribute to a More Accurate Indication for Prostate Biopsy
    biomedicines Article The Percentage of Free PSA and Urinary Markers Distinguish Prostate Cancer from Benign Hyperplasia and Contribute to a More Accurate Indication for Prostate Biopsy Zlata Huskova 1 , Jana Knillova 1, Zdenek Kolar 1, Jana Vrbkova 2, Milan Kral 3,* and Jan Bouchal 1,* 1 Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, 779 00 Olomouc, Czech Republic; [email protected] (Z.H.); [email protected] (J.K.); [email protected] (Z.K.) 2 Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech Republic; [email protected] 3 Department of Urology, University Hospital, 779 00 Olomouc, Czech Republic * Correspondence: [email protected] (M.K.); [email protected] (J.B.) Received: 28 April 2020; Accepted: 23 June 2020; Published: 25 June 2020 Abstract: The main advantage of urinary biomarkers is their noninvasive character and the ability to detect multifocal prostate cancer (CaP). We have previously implemented a quadruplex assay of urinary markers into clinical practice (PCA3, AMACR, TRPM8 and MSMB with KLK3 normalization). In this study, we aimed to validate it in a larger cohort with serum PSA 2.5–10 ng/mL and test other selected transcripts and clinical parameters, including the percentage of free prostate-specific antigen (PSA) (% free PSA) and inflammation. In the main cohort of 299 men, we tested the quadruplex transcripts. In a subset of 146 men, we analyzed additional transcripts (CD45, EPCAM, EZH2, Ki67, PA2G4, PSGR, RHOA and TBP). After a prostate massage, the urine was collected, RNA isolated from a cell sediment and qRT-PCR performed.
    [Show full text]
  • Mapping of Natural Signal Transduction Modulators on Drug Targets Relevant to Prostate Cancer Jayalakshmi T*1, P.B
    ISSN: 0974-2115 www.jchps.com Journal of Chemical and Pharmaceutical Sciences Mapping of Natural Signal Transduction Modulators on Drug Targets Relevant to Prostate Cancer Jayalakshmi T*1, P.B. Ramesh Babu2 and Revanth G3 1School of Bio-Engineering, Dept. of Genetic Engineering, Bharath Institute of Higher Education and Research Chennai, Tamil Nadu, India. 2HOD, School of Bio-Engineering, Dept. of Genetic Engineering, Bharath Institute of Higher Education and Research Chennai, Tamil Nadu, India. 3School of Bio-Engineering, Dept. of Bioinformatics, Bharath Institute of Higher Education and Research ,Chennai, Tamil Nadu, India. * Corresponding author: [email protected] ABSTRACT We have collected hundreds of natural signal transduction modulators from various science articles. During this study we've got projected to seek out the potential drug target for glandular carcinoma mistreatment the natural compounds. The procyanidin is that the effective natural signal transduction modulator for the cure of glandular carcinoma.FOLH1 factor is showing highest interactions, with the opposite glandular carcinoma genes. KEY WORDS: Cancerous cell, OMIM database, Protein, signal transduction. 1. INTRODUCTION Cancer: Cancer may be a term used for diseases within which abnormal cells divide while not management and are ready to invade different tissues. Cancer cells will unfold to different elements of the body through the blood and liquid body substance systems. Cancer isn't only unwellness however several diseases. There are quite one hundred differing types of cancer. Most cancers ar named for the organ or form of cell within which they begin - for instance, cancer that begins within the colon is termed carcinoma; cancer that begins in basal cells of the skin is termed basal cell cancer.
    [Show full text]
  • Comprehensive Resequence Analysis of a 97 Kb Region of Chromosome 10Q11.2 Containing the MSMB Gene Associated with Prostate Cancer
    Hum Genet (2009) 126:743–750 DOI 10.1007/s00439-009-0723-9 ORIGINAL INVESTIGATION Comprehensive resequence analysis of a 97 kb region of chromosome 10q11.2 containing the MSMB gene associated with prostate cancer Meredith Yeager Æ Zuoming Deng Æ Joseph Boland Æ Casey Matthews Æ Jennifer Bacior Æ Victor Lonsberry Æ Amy Hutchinson Æ Laura A. Burdett Æ Liqun Qi Æ Kevin B. Jacobs Æ Jesus Gonzalez-Bosquet Æ Sonja I. Berndt Æ Richard B. Hayes Æ Robert N. Hoover Æ Gilles Thomas Æ David J. Hunter Æ Michael Dean Æ Stephen J. Chanock Received: 30 June 2009 / Accepted: 17 July 2009 / Published online: 31 July 2009 Ó The Author(s) 2009. This article is published with open access at Springerlink.com Abstract Genome-wide association studies of prostate technology to resequence a *97-kb region that includes the cancer have identified single nucleotide polymorphism area surrounding MSMB (chr10: 51,168,025–51,265,101) in (SNP) markers in a region of chromosome 10q11.2, har- 36 prostate cancer cases, 26 controls of European origin, boring the microseminoprotein-b (MSMB) gene. Both the and 8 unrelated CEPH individuals in order to identify gene product of MSMB, the prostate secretory protein 94 additional variants to investigate in functional studies. We (PSP94) and its binding protein (PSPBP), have been pre- identified 241 novel polymorphisms within this region, viously investigated as serum biomarkers for prostate including 142 in the 51-kb block of linkage disequilibrium cancer progression. Recent functional work has shown that (LD) that contains rs10993994 and the proximal promoter different alleles of the significantly associated SNP in the of MSMB.
    [Show full text]
  • Mutation Analysis of the MSMB Gene in Familial Prostate Cancer
    British Journal of Cancer (2010) 102, 414 – 418 & 2010 Cancer Research UK All rights reserved 0007 – 0920/10 $32.00 www.bjcancer.com Mutation analysis of the MSMB gene in familial prostate cancer ,1 1 1 2 1 3 2 Z Kote-Jarai* , D Leongamornlert , M Tymrakiewicz , H Field , M Guy , AA Al Olama , J Morrison , L O’Brien1, R Wilkinson1, A Hall1, E Sawyer1, K Muir4, F Hamdy5, J Donovan6, D Neal7,8, D Easton3 and R Eeles1,9 1 2 Translational Cancer Genetics Team, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK; Department of Oncology. 3 University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK; CR-UK Genetic Epidemiology Unit, University of 4 Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK; University of Nottingham Medical School, Queens Medical Centre, Nottingham NG7 2UH, UK; 5Nuffield Department of Surgery, University of Oxford, Oxford OX3 9DU, UK; 6Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol, UK; 7Surgical Oncology (Uro-Oncology: S4), Departments of Oncology and Surgery, University of 8 Cambridge, Box 279, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK; Cancer Research UK Cambridge Research Institute & Li Ka 9 Shing Centre, Robinson Way, Cambridge CB2 0RE, UK; The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, UK & Fulham Road, London SW3 6JJ, UK BACKGROUND: MSMB, a gene coding for b-microseminoprotein, has been identified as a candidate susceptibility gene for prostate cancer (PrCa) in two genome-wide association studies (GWAS). SNP rs10993994 is 2 bp upstream of the transcription initiation site of MSMB and was identified as an associated PrCa risk variant.
    [Show full text]